Departamento de Oncología Médica y Radioterapia, Servicio Andaluz de Salud (SAS), Avenida de las Fuerzas Armadas 2, 18014 Granada, Spain.
Instituto de Investigación Biosanitaria, Ibis Granada, Hospital Universitario Virgen de las Nieves, Avenida de las Fuerzas Armadas 2, 18014 Granada, Spain.
Cells. 2020 Sep 2;9(9):2015. doi: 10.3390/cells9092015.
We have previously shown that the combination of radiotherapy with human umbilical-cord-derived mesenchymal stromal/stem cells (MSCs) cell therapy significantly reduces the size of the xenotumors in mice, both in the directly irradiated tumor and in the distant nonirradiated tumor or its metastasis. We have also shown that exosomes secreted from MSCs preirradiated with 2 Gy are quantitatively, functionally and qualitatively different from the exosomes secreted from nonirradiated mesenchymal cells, and also that proteins, exosomes and microvesicles secreted by MSCs suffer a significant change when the cells are activated or nonactivated, with the amount of protein present in the exosomes of the preirradiated cells being 1.5 times greater compared to those from nonirradiated cells. This finding correlates with a dramatic increase in the antitumor activity of the radiotherapy when is combined with MSCs or with preirradiated mesenchymal stromal/stem cells (MSCs*). After the proteomic analysis of the load of the exosomes released from both irradiated and nonirradiated cells, we conclude that annexin A1 is the most important and significant difference between the exosomes released by the cells in either status. Knowing the role of annexin A1 in the control of hypoxia and inflammation that is characteristic of acute respiratory-distress syndrome (ARDS), we designed a hypothetical therapeutic strategy, based on the transplantation of mesenchymal stromal/stem cells stimulated with radiation, to alleviate the symptoms of patients who, due to pneumonia caused by SARS-CoV-2, require to be admitted to an intensive care unit for patients with life-threatening conditions. With this hypothesis, we seek to improve the patients' respiratory capacity and increase the expectations of their cure.
我们之前已经表明，放射治疗联合人脐带源间充质基质/干细胞（MSCs）细胞治疗显著减少了异种肿瘤在小鼠中的大小，无论是在直接照射的肿瘤中还是在远处未照射的肿瘤或其转移灶中。我们还表明，经 2 Gy 预照射的 MSC 分泌的外泌体在数量、功能和质量上与非照射间充质细胞分泌的外泌体不同，并且 MSCs 分泌的蛋白质、外泌体和微泡在细胞被激活或未激活时会发生显著变化，与非照射细胞相比，预照射细胞中外泌体中的蛋白质含量增加了 1.5 倍。这一发现与放射治疗与 MSCs 或预照射间充质基质/干细胞（MSCs*）联合使用时抗肿瘤活性的显著增加相关。在对来自照射和未照射细胞的外泌体的负载进行蛋白质组学分析后，我们得出结论，膜联蛋白 A1 是两种状态下细胞释放的外泌体之间最重要和最显著的差异。鉴于膜联蛋白 A1 在控制急性呼吸窘迫综合征（ARDS）特征性的缺氧和炎症中的作用，我们设计了一种基于放射刺激的间充质基质/干细胞移植的治疗策略，以缓解因 SARS-CoV-2 引起的肺炎而需要入住生命危重症监护病房的患者的症状。通过这个假设，我们寻求提高患者的呼吸能力并增加他们治愈的期望。
